Type 1 multiple endocrine neoplasia (MEN1): contribution of genetic analysis to the screening and follow-up of a large French kindred.

OBJECTIVE

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal genetic disorder, the clinical phenotype of which includes tumours of the parathyroids and/or anterior pituitary and/or endocrine pancreas. The genetic defect has been mapped to the chromosome 11q13 and the MEN1 gene has been recently identified, thus allowing genetic screening in affected kindreds. The aim of this study was to establish the usefulness of genetic screening in the follow-up of a large MEN1 kindred.

PATIENTS

We describe a large kindred of 91 members, of whom 56 had clinical, biochemical and genetic screening. Twenty eight of them have been tested annually for the last 5 years.

RESULTS

Although the precise mutation is still undetermined in this kindred, genotypic determination confirmed linkage with the MEN1 gene in affected members and excluded 28 members from annual testing. By drawing our attention to susceptible subjects, genetic screening improved the evaluation of age-related penetrance of the disease in the 3 generations from this kindred. For instance, annual screening showed conversion from unaffected to affected phenotype in 4 subjects aged 14, 14, 15, and 17 years. Moreover, genetics helped us to evaluate the specificity of clinical or biochemical markers, and thus to discard useless investigations. So far however, the genetics have not helped to explain the phenotypic heterogeneity and particularly low incidence of pancreatic tumours in this kindred.

CONCLUSION

Genetic screening is very useful in detecting high risk individuals for MEN 1, since it avoids time-consuming and expensive investigations in non-affected subjects. By providing better understanding of the age-related penetrance of this syndrome, it improves the efficiency of screening. Genetic studies allow differentiation between clinical and biochemical features that are useful in follow-up and other confusing or unhelpful parameters.